AbMole丨Shikonin：从诱导细胞死亡程序到调节信号通路

Shikonin（紫草素，AbMole，M4240）是一种从紫草根中分离的萘醌类化合物，在多种研究中显示出广泛的生物活性。在细胞实验中，Shikonin对HTR-8/SVneo细胞的活力表现出浓度和时间依赖性抑制，其作用机制涉及诱导细胞的焦亡[1]。Shikonin（CAS No.：517-89-5）在胃癌NCI-N87细胞中，显著抑制细胞增殖，并影响凋亡相关蛋白Bax和Bcl-2的表达[2]。此外，Shikonin（紫草素）在SCLC细胞中通过抑制ERK信号通路和诱导铁死亡，显著抑制细胞增殖、迁移和侵袭[3]。在乳腺癌4T1细胞中，Shikonin通过诱导线粒体功能障碍和ROS产生抑制细胞增殖，并在小鼠原位模型中表现出肿瘤生长抑制和免疫调节作用[4]。

Shikonin在肾癌Caki-1和ACHN细胞中，通过浓度依赖性方式触发细胞坏死和凋亡，其作用可被N-乙酰半胱氨酸（Acetylcysteine，NAC，一种ROS清除剂）部分逆转。Shikonin（紫草素）在胰腺癌细胞中，通过抑制PAK1激酶活性（IC50为7.252 ± 0.054 μM）发挥抗肿瘤作用[5]。在动物实验中，Shikonin（50.0 mg/kg）通过调节miRNA-140-5p/TLR4信号通路在小鼠急性肺损伤模型中表现出显著的保护作用[6]。此外，Shikonin在胚绒毛尿囊膜（CAM）模型中通过抑制细胞增殖和诱导凋亡显著减少甲状腺髓样癌细胞的生长[7]。在神经炎症研究中，Shikonin通过抑制海马区炎症反应表现出抗抑郁和抗焦虑样作用[8]。这些研究揭示了Shikonin（紫草素，AbMole，M4240）在多种细胞模型（如HTR-8/SVneo、NCI-N87、HT29、4T1、Caki-1、ACHN等）和动物模型（如小鼠、鸡胚）中的广泛作用，其机制涉及焦亡、凋亡、铁死亡、ROS调节、信号通路抑制等多种途径。

参考文献及鸣谢

[1] Zeng, F.; Lai, Y.; Huang, Y.; et al. Shikonin from lithospermum erythrorhizon induces pyroptosis in trophoblast cells by activating the CTSB-NLRP3 inflammasome. Annals of medicine2024, 56 (1), 2394584.

[2] Jia, L.; Zhu, Z.; Li, H.; et al. Shikonin inhibits proliferation, migration, invasion and promotes apoptosis in NCI-N87 cells via inhibition of PI3K/AKT signal pathway. Artificial cells, nanomedicine, and biotechnology2019, 47 (1), 2662-2669.

[3] Qian, X.; Zhu, L.; Xu, M.; et al. Shikonin suppresses small cell lung cancer growth via inducing ATF3-mediated ferroptosis to promote ROS accumulation. Chemico-biological interactions2023, 382, 110588.

[4] Yu, C.; Xing, H.; Fu, X.; et al. Effect and mechanisms of shikonin on breast cancer cells in vitro and in vivo. BMC complementary medicine and therapies2024, 24 (1), 389.

[5] Ji, W.; Sun, X.; Gao, Y.; et al. Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer Cells. Molecules (Basel, Switzerland)2022, 27 (9).

[6] Zhang, Y. Y.; Liu, X.; Zhang, X.; et al. Shikonin improve sepsis-induced lung injury via regulation of miRNA-140-5p/TLR4-a vitro and vivo study. Journal of cellular biochemistry2020, 121 (3), 2103-2117.

[7] Hasenoehrl, C.; Schwach, G.; Ghaffari-Tabrizi-Wizsy, N.; et al. Anti-tumor effects of shikonin derivatives on human medullary thyroid carcinoma cells. Endocrine connections2017, 6 (2), 53-62.

[8] Shi, C.; Qi, Z.; Yang, C.; et al. Shikonin ameliorates depressive- and anxiogenic-like behaviors in rats via the suppression of inflammation in the hippocampus. Neuroscience letters2024, 837, 137893.